Abstract

Background

The phylogenetically highly conserved CK1 protein kinases consisting of at least seven
isoforms form a distinct family within the eukaryotic protein kinases. CK1 family
members play crucial roles in a wide range of signaling activities. However, the functional
role of CK1 in somatosensory pain signaling has not yet been fully understood. The
aim of this study was to clarify the role of CK1 in the regulation of inflammatory
pain in mouse carrageenan and complete Freund’s adjuvant (CFA) models.

Results

We have used two structurally different CK1 inhibitors, TG003 and IC261. TG003, which
was originally identified as a cdc2-like kinase inhibitor, had potent inhibitory effects
on CK1 isoforms in vitro and in cultured cells. Intrathecal injection of either TG003 (1-100 pmol) or IC261
(0.1-1 nmol) dose-dependently decreased mechanical allodynia and thermal hyperalgesia
induced by carrageenan or CFA. Bath-application of either TG003 (1 μM) or IC261 (1 μM)
had only marginal effects on spontaneous excitatory postsynaptic currents (sEPSCs)
recorded in the substantia gelatinosa neurons of control mice. However, both compounds
decreased the frequency of sEPSCs in both inflammatory pain models.

Conclusions

These results suggest that CK1 plays an important pathophysiological role in spinal
inflammatory pain transmission, and that inhibition of the CK1 activity may provide
a novel strategy for the treatment of inflammatory pain.